| Induction of senescence in human malignant glioma cells by p16INK4A. | |
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MedLine Citation:
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PMID: 9247304 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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p16INK4A is a G1-specific cell cycle inhibitor which maps to human chromosome 9p21, a region frequently mutated or deleted in cancer cell lines and primary tumors. In glioblastomas the frequency of homozygous deletions is 40-70% making it one of the most common mutations in this tumor type. We have analysed the significance of the loss of this gene in gliomas by introducing the cDNA for p16INK4A into the human glioma cell line U-1242 MG which has a deleted CDKN2 locus. We used the tetracycline repressible vector system and obtained two stably transfected clones that expressed p16INK4A upon induction. p16INK4A expression caused a G1 arrest and enlargement of the cells similar to that of senescent cells. When staining for Senescence-Associated beta-galactosidase activity, described to be specific for senescent cells, we could show that the enlarged cells specifically gave a positive staining reaction. This senescence phenotype was dependent on the continuous expression of p16INK4A since it was reversed upon reintroduction of tetracycline suppression. Thus, the induced expression of p16INK4A in these glioma cells reverted their immortal phenotype and caused an immediate cellular senescence. |
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Authors:
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L Uhrbom; M Nistér; B Westermark |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncogene Volume: 15 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 1997 Jul |
Date Detail:
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Created Date: 1997-08-28 Completed Date: 1997-08-28 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 505-14 Citation Subset: IM |
Affiliation:
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Department of Pathology, Uppsala University, University Hospital, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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genetics Carrier Proteins / genetics*, metabolism Cell Aging / genetics Cell Division / genetics Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinases / genetics, metabolism G1 Phase / genetics Gene Deletion Gene Expression Regulation, Neoplastic Genetic Vectors Glioma / drug therapy, genetics* Homozygote Humans Phenotype Proto-Oncogene Proteins* Retinoblastoma Protein / genetics, metabolism Tetracycline / pharmacology Vimentin / metabolism beta-Galactosidase / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Proto-Oncogene Proteins; 0/Retinoblastoma Protein; 0/Vimentin; 60-54-8/Tetracycline; EC 2.7.1.37/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 3.2.1.23/beta-Galactosidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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